Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death among women. Despite its immunogenicity, effective antitumor responses are limited, due, in part, to the presence of forkhead box protein 3–positive (Foxp3+) T regulatory (Treg) cells in the tumor microenvironment. However, the mechanisms that regulate the accumulation and the suppressive function of these Foxp3+ Treg cells are poorly understood. Here, we found that the majority of Foxp3+ Treg cells accumulating in the tumor microenvironment of EOCs belong to the subset of Foxp3+ Treg cells expressing inducible costimulator (ICOS). The expansion and the suppressive function of these cells were strictly dependent on ICOS-L costimulation provided by tumor plasmacytoid dendritic cells (pDC). Accordingly, ICOS+Foxp3+Treg cells were found to localize in close vicinity of tumor pDCs, and their number directly correlated with the numbers of pDCs in the tumors. Furthermore, pDCs and ICOS+ Foxp3+Treg cells were found to be strong predictors for disease progression in patients with ovarian cancer, with ICOS+Treg cell subset being a stronger predictor than total Foxp3+Treg cells. These findings suggest an essential role for pDCs and ICOS-L in immunosuppression mediated by ICOS+ Foxp3+ Treg cells, leading to tumor progression in ovarian cancer.

The pathogenesis of breast cancers that do not express estrogen receptors or Her-2/neu receptors (ERx/HER2x phenotype) is incompletely understood. We had observed markedly elevated gene expression of gamma-aminobutyric acid type A (GABA A ) receptor subunit p (GABAp, GABRP) in some breast cancers with ERx/HER2x phenotype. In this study, transcriptional profiles (TxPs) were obtained from 82 primary invasive breast cancers by oligonucleotide microarrays. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to measure GABAp gene expression in a separate cohort of 121 invasive breast cancers. GABAp gene expression values from TxP and RT-PCR were standardized and compared with clinicopathologic characteristics in the 203 patients. GABAp gene expression was increased in 16% of breast cancers (13/82 TxP, 20/ 121 RT-PCR), particularly in breast cancers with ERx/HER2x phenotype (60%), and breast cancers with basal-like genomic profile (60%). The profile of genes coexpressed with GABAp in these tumors was consistent with an immature cell type. In multivariate linear regression analysis, the level of GABAp gene expression was associated with ERx/HER2x phenotype (P<0.0001), younger age at diagnosis (P = 0.0003), and shorter lifetime duration of breastfeeding (£ 6 months) in all women (P = 0.017) and specifically in parous women (P = 0.013). GABAp gene expression was also associated with combinations of high grade with ERx/HER2x phenotype (P = 0.002), and with Hispanic ethnicity (P = 0.036). GABAp gene expression is increased in breast cancers of immature (undifferentiated) cell type and is significantly associated with shorter lifetime history of breastfeeding and with high-grade breast cancer in Hispanic women.

Objective This systematic review describes the efficacy, safety, and drug interactions of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose transport protein 2 (SGLT2) inhibitors in kidney transplant recipients (KTRs). Data Sources Articles were identified by English-language MEDLINE search, published prior to May 2020, using the terms kidney transplant, OR PTDM, OR NODAT, AND metformin, OR DPP4, OR GLP1, OR SGLT2. Study Selection and Data Extraction All selected studies were included if the study population was composed of adult KTRs who were diagnosed with either impaired glucose tolerance, diabetes mellitus (DM), new-onset diabetes after transplant (NODAT), or posttransplantation diabetes mellitus (PTDM). Data Synthesis In KTRs, there is evidence for safety with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors. However, urinary tract infections and a slight initial decrease in renal function may limit use of SGLT2 inhibitors. As compared with the nontransplant type 2 DM population, SGLT2 inhibitors are not as efficacious in KTRs. Relevance to Patient Care and Clinical Practice This review provides an overview of the current literature on newer antidiabetic agents, addressing efficacy, safety, and drug interactions to help guide clinical decision-making for their use in KTRs. Conclusion Newer antidiabetic agents have been recommended by the American Diabetes Association for potential cardiovascular, renal, and hypoglycemic benefits. Particular agents, such as DPP-4 inhibitors and GLP-1 RAs may play a role in correcting PTDM-related defects. Clinicians need to take into account both patient-specific and drug-specific characteristics when initiating these agents in KTRs.

Context.—Bone marrow (BM) examination is part of the staging workup of lymphoma patients. Few studies have compared BM histologic findings with results of flow cytometric immunophenotyping analysis in follicular lymphoma (FL) patients. Objective.—To correlate histologic findings with immunophenotypic data in staging BM biopsy and aspiration specimens of FL patients. Design.—Bone marrow biopsy specimens of untreated FL patients were reviewed. Histologic findings were correlated with 3-color flow cytometric immunophenotyping results on corresponding BM aspirates. Results.—Bone marrow biopsy specimens (with or without aspirates) of 114 patients with histologic evidence of FL in BM were reviewed. There were 76 bilateral and 38 unilateral biopsies performed, resulting in 190 specimens: 187 involved by FL and 3 negative (in patients with a positive contralateral specimen). The extent of BM involvement was &lt;5% in 32 (17.1%), ≥5% and ≤25% in 102 (54.6%), &gt;25% and ≤50% in 27 (14.4%), and &gt;50% in 26 (13.9%) specimens. The pattern of involvement was purely paratrabecular in 81 (43.3%), mixed in 80 (42.8%), and purely nonparatrabecular in 26 (13.9%). Immunophenotyping was only performed unilaterally, on BM aspirates of 92 patients, and was positive for a monoclonal B-cell population in 53 (57.6%) patients. Immunophenotyping was more often negative when biopsy specimens showed FL with a purely paratrabecular pattern. For comparison, we assessed 163 FL patients without histologic evidence of FL in BM also analyzed by flow cytometric immunophenotyping. A monoclonal B-cell population was identified in 5 patients (3%). Conclusions.—Our data suggest that 3-color flow cytometric immunophenotyping adds little information to the evaluation of staging BM specimens of FL patients.

Supplementary Tables 10-15 from Identification of a Clinically Relevant Androgen-Dependent Gene Signature in Prostate Cancer